When producing plastic containers including ampule products for foods, cosmetics or for medicinal purposes, in particular ophthalmics, parenterals or for artificial feeding, the microbiological quality of the filling material is critically important. The specifications set out in the international pharmacopoeia must be satisfied. A decisive factor is the sterility of the filling material before the filling, which can be achieved for example by sterile filtration. Another decisive factor is the sterility of the inner container surfaces of the plastic container products.
In this document, “microbiological contaminants” should be understood as a collective term to refer to bacteria, spores, yeasts, fungi, viruses and endotoxins, which were previously also referred to as pyrogens in technical parlance. The technical English term also used in this regard is “bioburden”.
The prior art has already provided suggestions for minimizing or largely preventing microbiological contaminants. For example, DE 10 2008 032 635 A1 describes a food and drink industry method and device for microbiologically optimized production of blow-molded plastic containers. That known solution involves the supply during the blowing operation for the plastic container of a medium, for example in the form of air, to the inside of the corresponding premolding, at a temperature of between 80° C. and 140° C. The heated air serves as a sterilization for the killing of bacteria. In order for this method to be effective, in view of the relatively low treatment temperatures, very long treatment times are required, certainly in the region of several hours, in order to sustainably prevent a build-up of bacteria.
DE 10 2011 008 132 A1 describes a method and a device for the production of blow-molded, at least partially sterile containers, in which a premolding made of a thermoplastic material is initially heated and is then stretched by a stretching rod and has a pressurized fluid applied to it. A sterilizing agent is additionally supplied in the region of the premolding. The known method preferably uses as a sterilization agent vaporized hydrogen peroxide, which is mixed with hot air, with the hydrogen peroxide concentration being approximately 15 to 35 percent by weight. The breakdown products of such chemical sterilization agents can contaminate the filling material and can have harmful toxicological consequences.
DE 695 20 445 T2 discloses a method and an associated device for the sterile packaging of a drink, in which, as part of the blow molding step for the container, the container is heated to a temperature sufficient to sterilize the inside of the container. Because a reliable sterilization requires temperatures significantly higher than 200° C. for a time period of several minutes, the choice of plastics for the container material for this known method is correspondingly limited. The polymers preferably used for the packaging of pharmaceuticals, such as polyethylene or polypropylene, can then not be used at all due to their low working or melting temperatures.
DE 10 2008 006 073 A1 discloses a so-called blow molding, filling and sealing production machine, which is particularly suitable for the production of filled containers for medicinal purposes. These containers include ampules as container products for eye drops with filling volumes of for example 0.1 ml to 10 ml, as well as ampules for injection solutions in the range of typically 0.5 ml to 50 ml. Standard clock speeds for the production of such filled and sealed blow molding, filling and sealing (BFS) containers are in the range of 10 to 18 seconds, whereas in modern systems of the type disclosed in DE 10 2008 006 073 A1 however, the cycle time is just 2 to 4 seconds. Due to these low cycle times alone, the use of the above-mentioned known sterilization methods is ruled out, which methods cannot be used for BFS methods because the container molding is immediately followed within a few seconds by the filling and a premolding or even an empty container is not available for a sterilization operation.
The microbiological status of containers produced according to the BFS method is described in the article by Frank Leo et al. “Evaluation of Blow-Fill-Seal Extrusion through Processing Polymer Contaminated with Bacterial Spores and Endotoxin”, published in the PDA Journal of Pharmaceutical Science and Technology Vol. 58, No. 3, May-June 2004, pages 147 to 158 for the particular case of a BFS system of type 624 by the company Weiler Engineering with cycle speeds of 12 to 18 seconds (see page 148). Amongst other things, the specialist article discloses that reduction of spores occurs by two possible mechanisms, either thermal deactivation resulting from the long-term influence of heat during production (see page 153, bottom left) or as a result of the achieved homogeneous distribution (see page 153, 5th paragraph) of the spores in the molten mass and an associated possible thermal inactivation. In spite of this achieved homogeneous distribution and the long residence time, the authors report only a small bacteria count reduction in the region of only 102 to 104 colony-forming units per gram (CFU/g).
The results described above are, as the authors explicitly state, not transferable to other systems, in particular not to those BFS systems with significantly lower residence times at a raised temperature, for example in the form of systems made by the company rommelag of type 460, which are the subject of the technical teaching according to DE 10 2008 006 073 A1. The clock speeds in those systems, as stated above, are typically in the region of less than 5 seconds. In these systems, no cutting of the warm polymer tube occurs, and the filling occurs by sterile filling tubes inside the intact plasticized polymer hose. The hose in any case then constitutes a sterile barrier relative to the exterior space or the environment.
Unfortunately it is not, however, always possible to ensure that the polymer granulate used for the BFS process has a sufficiently minimal microbiological contamination. It is then in practice possible, to some extent also as a result of incorrect transport, storage and handling of the plastic granulate, for microbiological contaminants, for example in the form of spores, to reach the granulate surface. The contaminants reaching the granulate surface can lead to an undesirably high microbiological contamination, which is not always reduced to an adequate extent by the previous BFS method according to the prior art.